Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization.

Autor:	Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Andrabi R; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA., Cottrell CA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Richey ST; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Song G; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA., Callaghan S; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA., Anzanello F; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA., Moyer TJ; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Abraham W; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Melo M; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Silva M; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Scaringi N; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Rakasz EG; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA., Sattentau QJ; Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK., Irvine DJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Burton DR; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. burton@scripps.edu andrew@scripps.edu.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. burton@scripps.edu andrew@scripps.edu.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; International AIDS Vaccine Initiative-Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Jul 28; Vol. 7 (31). Date of Electronic Publication: 2021 Jul 28 (Print Publication: 2021).
DOI:	10.1126/sciadv.abh2791
Abstrakt:	Rationally designed protein subunit vaccines are being developed for a variety of viruses including influenza, RSV, SARS-CoV-2, and HIV. These vaccines are based on stabilized versions of the primary targets of neutralizing antibodies on the viral surface, namely, viral fusion glycoproteins. While these immunogens display the epitopes of potent neutralizing antibodies, they also present epitopes recognized by non-neutralizing or weakly neutralizing ("off-target") antibodies. Using our recently developed electron microscopy polyclonal epitope mapping approach, we have uncovered a phenomenon wherein off-target antibodies elicited by HIV trimer subunit vaccines cause the otherwise highly stabilized trimeric proteins to degrade into cognate protomers. Further, we show that these protomers expose an expanded suite of off-target epitopes, normally occluded inside the prefusion conformation of trimer, that subsequently elicit further off-target antibody responses. Our study provides critical insights for further improvement of HIV subunit trimer vaccines for future rounds of the iterative vaccine design process. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
Databáze:	MEDLINE
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